Chronic kidney disease (CKD) is a highly prevalent condition with a high incidence (1, 2). Diabetes mellitus (DM), hypertension (HT), cardiovascular disease, metabolic syndrome, and obesity, are among the best known causes of CKD globally, with DM being the leading factor (1, 2).
However, in agricultural communities in Mesoamerica—a region and cultural area that begins in the southern part of North America and extends to the Pacific coast of Central America—as well as other regions of the world, heatstroke has been associated with CKD, along with other potential variables such as exposure to environmental toxins, infections, and genetic factors. Often, individuals are exposed to heatstroke and strenuous exercise during agricultural work, leading to dehydration that gradually causes kidney damage at the tubulointerstitial level (3). This entity is referred to as CKD of unknown origin (CKDu) or Mesoamerican nephropathy. Factors associated with kidney damage in CKDu include sustained dehydration, strenuous exercise, and rehydration with sweet and carbonated beverages. Additionally, social determinants such as poverty, low birth weight, and malnutrition contribute to the development of a slow, progressive, and irreversible form of CKD (3, 4) (Figure 1).
Mesoamerican nephropathy: What we know about the etiology and effects of consuming sugary drinks
Citation: Kidney News 16, 6
There is sufficient evidence that high consumption of sugary beverages is associated with DM, HT, obesity, and the consequent incidence and progression of CKD (5–7). Several indirect and direct mechanisms could explain this association. Sugary beverages contain added sugars and associated energy, which, when consumed regularly, lead to a high positive-energy balance, resulting in weight gain and obesity development. Obesity is a risk factor for DM, cardiovascular disease, and CKD. Additionally, these beverages, with high fructose as well as other sugars, can increase serum renin and urate concentrations, leading to interstitial fibrosis and renal vascular disease, all directly contributing to the development of kidney diseases (5).
On the other hand, in the physiology of CKDu, rehydration with sugary beverages after strenuous exercise and heatstroke exposure stimulates fructose activity, which generates inflammation, hypoxia, and tubular damage, increasing oxygen demand. In addition, this disrupts erythropoietin synthesis, causing anemia, which also increases tubular oxygen consumption. Tubular potassium reabsorption is also altered, leading to hypokalemia, which limits angiogenesis, further affecting oxygen consumption. All of this causes tubulointerstitial damage, which, with continued exposure to heat and probably other insults such as environmental toxins, produces chronic tubulointerstitial damage. This repeated damage leads to a slow, progressive, and asymptomatic form of CKD in the young population of the agricultural zones of Mesoamerica. Furthermore, fructose activation is also implicated in kidney damage in this population. Additionally, there is a local accumulation of uric acid, which induces hypoxia, inflammation, and general tubular damage (8–10) (Figure 2).
Pathophysiology of CKDu: Sugar liquid intake and kidney risk
Citation: Kidney News 16, 6
Among the actions proposed to prevent and delay the progression of kidney damage are: 1) removing the individual from the risk area, 2) ensuring adequate hydration with electrolyte-based solutions, 3) increasing the periods of rest in the shade, and 4) rehydrating during work. Due to the potential involvement of uric acid in the pathophysiology of the disease, the use of allopurinol has also been proposed to mitigate kidney damage (11, 12).
The hydration pattern of individuals, especially those with risk factors for developing CKD, should be based on healthy fluids with a good electrolyte content and low sugar.
Footnotes
References
- 1.↑
Shlipak MG, et al. The case for early identification and intervention of chronic kidney disease: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2021; 99:34–47. doi: 10.1016/j.kint.2020.10.012
- 2.↑
Correa-Rotter R, et al. Unmet needs of CKD in Latin America: A review from expert virtual working group. Kidney Int Rep 2023; 8:954–967. doi: 10.1016/j.ekir.2023.02.1082
- 3.↑
Sanchez Polo V, et al. Mesoamerican nephropathy (MeN): What we know so far. Int J Nephrol Renovasc Dis 2020; 13:261–272. doi: 10.2147/IJNRD.S270709
- 4.↑
Correa-Rotter R, et al. CKD of unknown origin in Central America: The case for a Mesoamerican nephropathy. Am J Kidney Dis 2014; 63:506–520. doi: 10.1053/j.ajkd.2013.10.062
- 5.↑
Rebholz C, et al. Patterns of beverages consumed and risk of incident kidney disease. Clin J Am Soc Nephrol 2019; 14:49–56. doi: 10.2215/CJN.06380518
- 6.
van Westing AC, et al. Diet and kidney function: A literature review. Curr Hypertens Rep 2020; 22:14. doi: 10.1007/s11906-020-1020-1
- 7.↑
Heo GY, et al. Sweetened beverage intake and incident chronic kidney disease in the UK Biobank Study. JAMA Netw Open 2024; 7:e2356885. doi: 10.1001/jamanetworkopen.2023.56885
- 8.↑
Roncal Jimenez CA, et al. Fructokinase activity mediates dehydration-induced renal injury. Kidney Int 2014; 86:294–302. doi: 10.1038/ki.2013.492
- 9.
Hansson E, et al. Pathophysiological mechanisms by which heat stress potentially induces kidney inflammation and chronic kidney disease in sugarcane workers. Nutrients 2020; 12:1639. doi: 10.3390/nu12061639
- 10.↑
Roncal-Jimenez C, et al. Heat stress nephropathy from exercise-induced uric acid crystalluria: A perspective on Mesoamerican nephropathy. Am J Kidney Dis 2016; 67:20–30. doi: 10.1053/j.ajkd.2015.08.021
- 11.↑
Wegman D, et al.; Work Health and Efficiency (WE) Program Working Group. Intervention to diminish dehydration and kidney damage among sugar cane workers. Scand J Work Environ Health 2018; 44:16–24. doi: 10.5271/sjweh.3659
- 12.↑
Roncal-Jimenez CA, et al. Experimental heat stress nephropathy and liver injury improved by allopurinol. Am J Physiol Renal Physiol 2018; 315:F726–F733. doi: 10.1152/ajprenal.00543.2017
